Human malaria is caused by four species of Plasmodium, P. falciparum, P. vivax, P. ovale and P. malariae. According to a report of the World Health Organization (WHO) published 1986, there occur every year worldwide nearly a hundred million cases of malaria infection, of which about one million, mostly young children infected with P. falciparum, fatal. Due partly to the appearance of drug-resistant parasites and insecticide-resistant mosquito vectors, the incidence of malaria has been increasing. For example, Indian health authorities reported about 100,000 cases of malaria in 1962 and 3 million (mostly due to P. vivax) in 1980 (Bruce-Chwatt, Essential Malariology, 2nd edn., Heinemann, London [1985]).
New technical developments have raised hopes that it will become soon possible to produce anti-malaria vaccines which can help to counter the spread of malaria. First, new methods of vaccine development (involving, for example, gene cloning, use of monoclonal antibodies for antigen identification, and immunization with synthetic peptides) can be applied to the case of malaria. Second, long-term cultures of P. falciparum in human red blood cells (Trager et al., Science 193, 673-675 [1976]) have provided a ready source of material for the study of the parasite. More recently, it has become possible to maintain all stages of the parasite's life cycle in the laboratory (Ponnudurai et al., Trans. R. Soc. Trop. Med. Hyg. 76, 812-818 [1982]; Mazier et al., Science 227, 440-442 [1985]).
P. falciparum spends part of its life-cycle in human red blood cells. A merozoite invades the host cell, enlarges and later undergoes repeated nuclear division to form a schizont. Maturation of the schizont yields a new crop of merozoites which are released into the blood stream and, after a short time, reinvade new erythrocytes.
A protein has been detected on the surface of merozoites and schizonts which could be active as a vaccine against malaria. When synthesized, the protein has an apparent molecular weight of 190,000-200,000 D (Perrin et al., Clin. Exp. Immunol. 41, 91-96 [1980]; Holder et al., J. Exp. Med. 156, 1528-1538 [1982]; Hall et al., Mol. Biochem. Parasitol. 7, 247-265 [1983] and Mol. Biochem. Parasitol. 11, 61-80 [1984]). It has been called GP185, p190, 195-kD protein and polymorphic schizont antigen (PSA). In addition, much, but not all of the protein is lost when merozoites invade new erythrocytes (Holder et al., supra; Hall et al., supra [1983]).
Analogues of p190 are present in all known species of Plasmodium. In all cases tested antibodies against p190 block parasite invasion in vitro (Epstein et al., J. Immunol. 127, 212-217 [1981]; perrin et al., J. Exp. Med. 160, 441-451 [1984]; Boyle et al., Infect. Immun. 38, 94-102 [1982]). Injection of purified p190 protein in Saimiri monkeys leads to at least partial protection against malaria (Hall et al., supra [1984]; Perrin et al., supra [1984]). The gene encoding the p190 protein has been isolated and sequenced from three different parasite isolates, namely the Thai isolate K1 (Mackay et al., EMBO J. 4, 3823-3829 [1985]), the Malaysian isolate CAMP (Weber et al., Nucleic Acids Res. 14, 3311-3323 [1986]) and the West African isolate Wellcome (Holder et al., Nature 317, 270-273 [1985]). Sequence comparisons between these alleles have shown that there is a certain degree of polymorphism between the different isolates. The tripeptide repeats found near the amino-terminus of each allele for example are different in each case studied.
For the development of a vaccine it is necessary to find an epitope on p190 which is present in most or preferably in all isolates, to protect against a wide variety of parasite variants.